It is widely recognized that interactive homeostatic mechanisms exist between cells from the time of blastula formation, but little is known of how such non-immune and immune surveillance mechanisms might interface to control the emergence of malignant growths. I have preliminary evidence that mammary tumors grow much more readily in mammary fatpads than at subcutaneous sites and prefer intact mammary fatpads to cleared fatpads which are devoid of mammary glandular elements. I wish to investigate mammary tumors growing in their natural anatomic site to determine both the mechanism of this site preference and its consequences. The study of the mechanism will focus on cellular interactions within the mammary gland fatpad. Interactions between tumor cells and non-lymphoid cells (normal ductal tissue, pre-neoplastic lesions, and other mammary tumors), between tumor and lymphoid cells, and between lymphoid and non-lymphoid cells of the mammary gland will be investigated both in vitro and in vivo. The studies of the consequences of site preference will include determination of relationship to clinical parameters such as growth rates, invasiveness, and metastatic potential of a series of tumors and testing of the relative susceptibilities to chemotherapy of tumors growing in different sites.